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The first empirical attempts of a pharmacological treatment of Parkinson's disease (PD) were made in the 1860s by Ordenstein and Charcot in Paris by using extracts from Hyscyamus niger,Atropia belladonna, and Datura stramonium containing the anticholinergic compounds hyoscine and scopolamine.1,2 With the development of synthetic anticholinergic drugs in the 1940s3 these agents became the mainstay of antiparkinsonian drug treatment. However, while improving tremor and rigidity, they had little effect on akinesia.4

The classical experiments on reserpinized animals by Carlsson in 1957, which showed that the akinesia of catecholamine-depleted animals could be reversed by levodopa (L-dopa) administration,5 led to the hypothesis of a dopaminergic disorder as the pathophysiological basis of PD. Shortly afterwards, the finding in postmortem studies of dopamine deficiency in the striatum of PD patients, by Ehringer and Hornykiewicz in Vienna in 1960,6 and the observation of reduced dopamine excretion in the urine of PD patients, by Barbeau and colleagues,7 marked the beginning of a new “era” in the treatment of PD. In 1961, two groups in Vienna and Montreal independently reported positive results of open-label small-scale clinical trials with L-dopa in parkinsonian patients.8,9 Five years later, Cotzias and colleagues demonstrated striking efficacy of high-dose oral L-dopa,10 the potentiation of its effects and the improvement of side effects with coadministration of peripheral dopa decarboxylase inhibitors (DCIs),11 as well as the long-term side effects of L-dopa treatment.12

Until today L-dopa substitution has remained the gold standard of antiparkinsonian drug therapy, although important advances have been made, including the introduction of directly acting dopamine agonists and MAO-B inhibitors. L-dopa treatment of PD, however, has also introduced new therapeutic challenges such as response fluctuations and drug-induced dyskinesias, which have not only prompted the continuing development of novel pharmacokinetic formulations and delivery systems for L-dopa itself but also focussed drug development efforts on nondopaminergic systems. Finally, the progression of PD is associated with a plethora of nonmotor symptoms, which can make advanced PD one of the most complex therapeutic scenarios in neurology.

This chapter first summarizes medical treatment options to control motor symptoms both in early and in advanced disease and will then move on to describe the pharmacological management of the most common nonmotor problems of this illness.

This section reviews the most commonly used drugs to treat the motor symptoms of PD both for initial monotherapy in early PD and for the management of L-dopa-related motor complications in advanced PD. For each stage, drugs are reviewed by class of agents. For each drug, a brief synopsis of its pharmacology and mechanism of action is followed by a summary of the available evidence for efficacy from controlled clinical trials, a review of safety data, closing with recommendations for clinical use by North American and European guidelines.